Gemcitabine plus split-dose cisplatin could be a promising alternative to gemcitabine plus carboplatin for cisplatin-unfit patients with advanced urothelial carcinoma

Cancer Chemother Pharmacol. 2015 Jul;76(1):141-53. doi: 10.1007/s00280-015-2774-z. Epub 2015 May 23.

Abstract

Purpose: Cisplatin-based chemotherapies are standard treatment regimens of advanced urothelial cell carcinoma. But a significant proportion of patients are unsuitable for cisplatin due to impaired renal function. Carboplatin-based regimens such as gemcitabine and carboplatin regimen (GCb) were applied due to less nephrotoxicity and side effects in these patients. However, it is known that clinical outcome of carboplatin-based regimens was unsatisfactory compared to cisplatin-based regimens. We compared the nephrotoxicity and response to treatment between GCb and gemcitabine plus split-dose cisplatin regimen (GC-S).

Methods: GC-S consists of cisplatin 35 mg/m(2) given on day 1, 2 and gemcitabine 1000 mg/m(2) on day 1, 8 every 3 weeks. GCb consists of carboplatin (AUC 4.5) on day 1 and gemcitabine 1000 mg/m(2) on day 1, 8 every 3 weeks. Patient demographics, serum creatinine and calculated GFR, adverse events, and radiologic response were retrospectively reviewed.

Results: Forty-four patients with advanced urothelial carcinoma treated with GCb (n = 22) or GC-S (n = 22) in our institution. There was no difference at deterioration of serum creatinine or GFR between GCb and GC-S (p = 0.442, p = 0.345). For patients who had GFR < 60 mL/min/1.73 m(2) subgroup, similar results were produced (p = 0.292, p = 0.186). In addition, GC-S (68.4 %) showed improved response compared to GCb (31.6 %) (p = 0.023). Both treatments were well tolerated, and there were no unexpected serious adverse events.

Conclusions: Based on preserved renal function, favorable response, and tolerability, GC-S could be a promising alternative to GCb for cisplatin-unfit patients with advanced urothelial carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Carboplatin / administration & dosage
  • Carboplatin / adverse effects
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives
  • Drug Administration Schedule
  • Female
  • Gemcitabine
  • Humans
  • Male
  • Middle Aged
  • Retrospective Studies
  • Treatment Outcome
  • Urologic Neoplasms / drug therapy*

Substances

  • Deoxycytidine
  • Carboplatin
  • Cisplatin
  • Gemcitabine